Molecular imaging is the in vivo study and measurement of biological processes at the molecular level (1). Nuclear Magnetic Resonance (NMR) Imaging, or Magnetic Resonance Imaging (MRI) as it is commonly known, is a non-invasive imaging modality that can produce high resolution, high contrast images of the interior of a subject. MRI involves the interrogation of the nuclear magnetic moments of a sample placed in a strong magnetic field with radio frequency (RF) magnetic fields. During MRI the subject, typically a human patient, is placed into the bore of an MRI machine and is subjected to a uniform magnetic field B0 produced by a polarizing magnet housed within the MRI machine. Radio frequency (RF) pulses, generated by RF coils housed within the MRI machine in accordance with a particular localization method, are typically used to scan target tissue of the patient. MRI signals are radiated by excited nuclei in the target tissue in the intervals between consecutive RF pulses and are sensed by the RF coils. During MRI signal sensing, gradient magnetic fields are switched rapidly to alter the uniform magnetic field at localized areas thereby allowing spatial localization of MRI signals radiated by selected slices of the target tissue. The sensed MRI signals are in turn digitized and processed to reconstruct images of the target tissue slices using one of many known techniques.
When a target substance, such as human tissue, is subjected to the static polarizing magnetic field B0, the individual magnetic moments of the spins in the tissue attempt to align with the static polarizing magnetic field B0, but precess about the static polarizing magnetic field B0 in random order at their characteristic Larmor frequency. The net magnetization vector lies along the direction of the static polarizing magnetic field B0 and is referred to as the equilibrium magnetization M0. In this configuration, the Z component of the magnetization or longitudinal magnetization MZ is equal to the equilibrium magnetization M0. If the target tissue is subjected to an excitation magnetic field B1, which is in the x-y plane and which is near the Larmor frequency, the longitudinal magnetization MZ may be rotated, or “tipped” into the x-y plane to produce a net transverse magnetic moment MXY. When the excitation magnetic field B1 is terminated, relaxation of the excited spins occurs, with a signal being emitted that effects the magnitude of radiated MRI signals. The emitted signal is received and processed to form an image.
In particular, when the excitation magnetic field B1 is terminated, the longitudinal magnetization MZ relaxes back to its equilibrium. The time constant that describes how the longitudinal magnetization MZ returns to its equilibrium value is commonly referred to as the spin lattice relaxation time T1. The spin lattice relaxation time T1 characterizes the time required to reduce the difference between the longitudinal magnetization MZ and its equilibrium longitudinal magnetization value M0 to zero.
The net transverse magnetic moment MXY also relaxes back to its equilibrium when the excitation magnetic field B1 is terminated. The time constant that describes how the transverse magnetic moment MXY returns to its equilibrium value is commonly referred to as transverse relaxation time or spin-spin relaxation time T2. The transverse relaxation time T2 characterizes the time required to reduce the transverse magnetic moment MXY to zero. Both the spin lattice relaxation time T1 and the transverse relaxation time T2 are tissue specific and vary with concentration of different chemical substances in the tissue as well as with different microstructural features of the tissue. Variations of the spin lattice relaxation time T1 and/or the transverse relaxation time T2 from normal can also be indicative of disease or injury.
Like many diagnostic imaging modalities, MRI can be used to differentiate tissue types, e.g. muscles from tendons, white matter from gray matter, healthy tissue from pathologic tissue, etc. There exist many different MRI techniques, the utility of each depending on the particular tissues under examination. Some techniques examine the rate of tissue magnetization, while others measure the amount of bound water or the velocity of blood flow. Often, several MRI techniques are used together to improve tissue identification. In general, the greater the number of identification methods available the better chance of identifying a certain tissue type or pathology.
In some instances, contrast agents or contrast materials may be used to emphasize certain anatomical regions. For example, a Gadolinium chelate injected into a blood vessel will produce enhancement of the vascular system, or the presence and distribution of leaky blood vessels. Iron-loaded stem cells, injected into the body and detected by MRI, will allow stem cell migration and implantation in vivo to be tracked.
Contrast agents can enhance imaging of target sites or tissues through the complementary processes of accumulation and activation. Accumulation occurs when the local concentration of the contrast agent is increased through metabolic uptake or molecular adhesion leading to localized image enhancement. A growing number of contrast agents are also activatable, their behavior mediated by interaction with a target molecule, such as a specific protein or macromolecule. Contrast agents demonstrating activation are interchangeably called “sensing”, “smart”, or “activatable” contrast agents.
Activatable contrast agents are used in MRI studies to improve the specificity of the contrast agent (2). Ideally activatable contrast agents produce no image enhancement in the inactivated state; however, to date, these contrast agents combined with conventional MRI have shown image intensity enhancement in both inactivated and activated states, with relatively modest signal intensity ratios between these two states.
Accordingly, there is a continuing need for improvements in MRI. It is therefore an object of an aspect to provide a novel system and method for producing image contrast in magnetic resonance imaging.